The immunobiological relationship between host and parasite in African trypanosomiasis is the focus of this proposal. Recent evidence suggests that macrophage activation is associated with regulation of T cell responses as well as development of host resistance during infection. Accordingly we hypothesize that events controlling macrophage activation influence the course of infection. Thus, the cellular and molecular mechanisms that affect macrophage activation and parasite antigen specific T cell stimulation in infected animals, and the immunological consequences of such events, comprise the specific aims of the project. An experimental model system of the human disease will be studied in which inbred strains of mice differing in immune responsiveness and susceptibility are infected with well characterized Trypanosoma brucei rhodesiense clones that express different antigenic and biological traits.